We wish to determine the in vivo and in vitro interactons with mammalian DNA of (a) the antineoplastic drug cis-DDP and, (b) analogous ruthenium (Ru) amine and nitrosyl compounds synthesized in this laboratory. First, using chemical and biophysical techniques, the kinds of reactions of cis-DDP and ruthenium compounds with DNA will be documented. These studies will be performed using exact molar ratios of drugs to DNA. Thus, the stoichiometry, kinetics and specificity of their reactions with DNA and chromatin will be determined. The biological studies outlined are designed to test our working hypothesis on the increased sensitivity of new DNA and high G-C DNA to platinization. Information obtained from the platinum drug studies will be used in a program for biophysical analysis as well as for screening ruthenium compounds for potential antitumor activity. The ruthenium compounds will be examined for pharmacological activity by testing various doses of the compounds for: (a) toxicity to primary and transformed cell lines in tissue culture, (b) inhibition of DNA, RNA or protein synthesis in such cells, and (c) inhibition of growth of KB (human nasopharangeal carcinoma) cells in suspension culture. BIBLIOGRAPHIC REFERENCES: Stone, P.J., Kelman, A.D., Sinex, F.M., Bhargava, M.M. and Halvorson, H.O. DNA base composition and sequence dependent binding of the antitumor drug cis-Pt(NH3)2C12. Improves resolution of alpha, beta and gamma DNAs of yeast. J. Mol. Biol. 104:793 (1976). Clarke, M.J., Kelman A.D. and Buchbinder, M. Interactions of amineruthenium (II and III) complexes with DNA. American Chemical Society Abstracts, 172nd National Meeting (1976).